During the past year we have completed our studies concerning the question of whether any member of the retrovirus family might be involved in the pathogenesis of Multiple Sclerosis. Using PCR primers specific for both spuma, HTLV-1, HTLV-2 and a general probe for the retroviral family, we were unable to find DNA evidence of these viruses in the brains of 23 MS patients and an equal number of non-MS brains. A manuscript describing these findings has been completed and submitted to the J. Neurovirology. We have since turned our attention to another virus HHV-6 which is a member of the herpes virus family and recently shown to be the cause of childhood Roseola. These viruses are well known to remain latent in tissues for long periods of time only to be reactivated by a number of internal and external factors. A recent report by Challoner et al. (1995) in which probes specific for HHV-6 detected HHV-6 viral DNA in an equal number of MS and non-MS brains. However immunohistochemical studies of the brains with an anti-HHV-6 antibody revealed the presence of HHV-6 proteins in the oligodentrocytes of MS patients but not in other neurological control brains. Based on these findings we have essentially confirmed their results. PCR analysis on 8 MS brains revealed that 5/8 were positive for HHV-6 DNA in the plaque and periplaque areas of the brain. Only 2/12 non-MS brains were positive. More significant was our finding that immunohistochemical studies revealed that 7/13 MS brains were positive for the structural protein of HHV-6 in oligodendrocytes while none of the non-MS brains were positive (0/10). Examination of the sera of MS patients revealed that 12/20 sera tested had IgM antibodies to HHV-6 compared to 1/20 control sera. CSF studies of IgG and IgM antibodies to HHV-6 were negative in these patients suggesting primarily a peripheral reaction to this virus. Our plans for future studies are as follows: 1) We will test new monoclonal antibodies to other HHV-6 proteins in MS brains and non-MS controls. 2) We will increase the number of sera tested for the presence of HHV-6 antibodies. 3) We will use a recently developed antigen capture ELISA kit to determine whether HHV-6 antigen is circulating in the sera of MS patients. 4) Finally we are considering a clinical trial with gancyclovir (known to inhibit HHV-6 growth in vitro) in MS patients.